Disease-specific profiles of apathy in Alzheimer’s disease and behavioural-variant frontotemporal dementia differ across the disease course
Abstract
Apathy is one of the most prevalent and disabling non-cognitive symptoms of dementia. This loss of motivation and pervasive decline in goal-directed behaviour represents a core diagnostic feature of behavioural-variant frontotemporal dementia (bvFTD) and is also common in Alzheimer's disease (AD). However, despite growing recognition of a multidimensional model, apathy has typically been examined as a unitary symptom. Here, we employed a cross-sectional design to characterise the multidimensional nature of apathy across syndromes and disease course. 92 participants (44 bvFTD, 20 AD, 28 controls) completed the Dimensional Apathy Scale (DAS) to quantify emotional, executive, and initiation apathy. Patients were divided into early and late stages based on time since symptom onset. All participants underwent structural MRI and voxel-based morphometry was used to identify neural correlates of apathy dimensions. In the early stage of the disease (< 5 years since onset), emotional apathy was greater in bvFTD than AD. In contrast, in the late stage (> 5 years since onset), executive apathy was greater in AD than bvFTD, although apathy was elevated across all dimensions compared to controls. Notably, apathy was observed in the absence of self-reported depression in 46.2% of patients, with no patients classified as depressed only. Neuroimaging analyses revealed both common and divergent prefrontal and subcortical neural correlates associated with apathy dimensions. Our results reveal differing profiles of apathy across the disease course, in AD and bvFTD, with distinct brain regions mediating these dimensions. These findings will inform the development of appropriate treatment targets to ameliorate the impact of apathy in dementia.
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Disease progression in bvFTD has been associated with various behavioral changes, from an increase in core features to specific changes, that correlate with FTD-specific progression measures.
“Disease progression in bvFTD has been associated with various behavioral changes, from an increase in core features, e.g., decreased socio-emotional abilities and increased multi-dimensional apathy, to specific changes, e.g., increased fat preference and hypersensitivity to loud noises (Midorikawa et al., 2016; Wei et al., 2020; Ahmed et al., 2021; Foster et al., 2022), that correlate with FTD-s”
From The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials (2024) · cites this paper as Wei et al., 2020
A cross-sectional study showed an increase of DAS scores during the disease course of bvFTD, distinguishing emotional apathy in early (<5 years) and executive apathy in later stages (>5 years), associated with distinct neurobiological substrates.
“A cross-sectional study on apathy profiles during disease course of bvFTD, showed an increase of DAS scores, while distinguishing emotional apathy in early (<5 years) and executive apathy in later stages (>5 years), associated with distinct neurobiological substrates (Wei et al., 2020).”
From The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials (2024) · cites this paper as Wei et al., 2020
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Correlation of Alzheimer’s Disease and Other Psychological and Non-Psychological Conditions
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Regional brain abnormalities in behavioral variant frontotemporal dementia: a meta-analysisPreprint
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Risky decision-making in dementia: Exploring neural correlates and related clinical symptoms
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Self-citation
- Authors
- Wei, G., Irish, M., Hodges, J. R., Piguet, O., & Kumfor, F.
- Affiliations
- The University of Sydney (AU)
- Corresponding author
- Kumfor, Fiona
- Venue
- Journal of Neurology
- Published
- 2019-12-23
- Volume
- 267
- Issue
- 4
- Pages
- 1086-1096
- ISSN
- 0012-1037 (ISSN-L)
- 0340-5354
- 1432-1459
- OpenAlex
- W2995342297
- Cited by
- 54
- References
- 49
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 6 · 2023: 8 · 2022: 10 · 2021: 12 · 2020: 4
- FWCI
- 5.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health and Medical Research Council (GNT1037746, GNT1121791, GNT1106031, GNT1103258)
- Australian Research Council (FT160100096)
- Dementia Australia Research Foundation
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Social Sciences › Psychology › Clinical Psychology › Historical and Modern Theater Studies
- Keywords
- apathy, Alzheimer's disease, behavioral variant frontotemporal dementia, emotional apathy, clinical course, prefrontal cortex, subcortical structures, goal-directed behavior
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cross-Sectional Studies, Depression, Emotions, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Disease Progression, Executive Function, Frontotemporal Dementia, Apathy, Gray Matter
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